Showing papers by "University of British Columbia published in 2006"
TL;DR: It is revealed that the current Health Canada physical activity guidelines are sufficient to elicit health benefits, especially in previously sedentary people, and that a further increase in physical activity and fitness will lead to additional improvements in health status.
Abstract: The primary purpose of this narrative review was to evaluate the current literature and to provide further insight into the role physical inactivity plays in the development of chronic disease and premature death. We confirm that there is irrefutable evidence of the effectiveness of regular physical activity in the primary and secondary prevention of several chronic diseases (e.g., cardiovascular disease, diabetes, cancer, hypertension, obesity, depression and osteoporosis) and premature death. We also reveal that the current Health Canada physical activity guidelines are sufficient to elicit health benefits, especially in previously sedentary people. There appears to be a linear relation between physical activity and health status, such that a further increase in physical activity and fitness will lead to additional improvements in health status.
6,852 citations
TL;DR: In this article, a simple cosmological model with only six parameters (matter density, Omega_m h^2, baryon density, BH density, Hubble Constant, H_0, amplitude of fluctuations, sigma_8, optical depth, tau, and a slope for the scalar perturbation spectrum, n_s) was proposed to fit the three-year WMAP temperature and polarization data.
Abstract: A simple cosmological model with only six parameters (matter density, Omega_m h^2, baryon density, Omega_b h^2, Hubble Constant, H_0, amplitude of fluctuations, sigma_8, optical depth, tau, and a slope for the scalar perturbation spectrum, n_s) fits not only the three year WMAP temperature and polarization data, but also small scale CMB data, light element abundances, large-scale structure observations, and the supernova luminosity/distance relationship. Using WMAP data only, the best fit values for cosmological parameters for the power-law flat LCDM model are (Omega_m h^2, Omega_b h^2, h, n_s, tau, sigma_8) = 0.1277+0.0080-0.0079, 0.02229+-0.00073, 0.732+0.031-0.032, 0.958+-0.016, 0.089+-0.030, 0.761+0.049-0.048). The three year data dramatically shrink the allowed volume in this six dimensional parameter space. Assuming that the primordial fluctuations are adiabatic with a power law spectrum, the WMAP data_alone_ require dark matter, and favor a spectral index that is significantly less than the Harrison-Zel'dovich-Peebles scale-invariant spectrum (n_s=1, r=0). Models that suppress large-scale power through a running spectral index or a large-scale cut-off in the power spectrum are a better fit to the WMAP and small scale CMB data than the power-law LCDM model: however, the improvement in the fit to the WMAP data is only Delta chi^2 = 3 for 1 extra degree of freedom. The combination of WMAP and other astronomical data yields significant constraints on the geometry of the universe, the equation of state of the dark energy, the gravitational wave energy density, and neutrino properties. Consistent with the predictions of simple inflationary theories, we detect no significant deviations from Gaussianity in the CMB maps.
6,002 citations
TL;DR: It is shown that TDP-43 is the major disease protein in both frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis.
Abstract: Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.
5,440 citations
University of Tennessee1, Oak Ridge National Laboratory2, West Virginia University3, Umeå University4, University of British Columbia5, United States Department of Energy6, Ghent University7, Swedish University of Agricultural Sciences8, Institut national de la recherche agronomique9, Virginia Tech10, Michigan Technological University11, University of Toronto12, Pennsylvania State University13, University of Provence14, University of Georgia15, University of Florida16, University of California, Berkeley17, Lawrence Berkeley National Laboratory18, University of Arizona19, Purdue University20, Stanford University21, United States Department of Agriculture22, University of Turku23, University of Helsinki24, Massachusetts Institute of Technology25, University of Tennessee Health Science Center26, University of Tübingen27
TL;DR: The draft genome of the black cottonwood tree, Populus trichocarpa, has been reported in this paper, with more than 45,000 putative protein-coding genes identified.
Abstract: We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.
4,025 citations
Dalhousie University1, University of Wyoming2, Plymouth Marine Laboratory3, Stockholm University4, Royal Swedish Academy of Sciences5, University of California, Santa Barbara6, Scripps Institution of Oceanography7, Smithsonian Tropical Research Institute8, Stanford University9, University of California, Davis10, University of British Columbia11
TL;DR: The authors analyzed local experiments, long-term regional time series, and global fisheries data to test how biodiversity loss affects marine ecosystem services across temporal and spatial scales, concluding that marine biodiversity loss is increasingly impairing the ocean's capacity to provide food, maintain water quality, and recover from perturbations.
Abstract: Human-dominated marine ecosystems are experiencing accelerating loss of populations and species, with largely unknown consequences. We analyzed local experiments, long-term regional time series, and global fisheries data to test how biodiversity loss affects marine ecosystem services across temporal and spatial scales. Overall, rates of resource collapse increased and recovery potential, stability, and water quality decreased exponentially with declining diversity. Restoration of biodiversity, in contrast, increased productivity fourfold and decreased variability by 21%, on average. We conclude that marine biodiversity loss is increasingly impairing the ocean's capacity to provide food, maintain water quality, and recover from perturbations. Yet available data suggest that at this point, these trends are still reversible.
3,672 citations
TL;DR: Basal-like breast tumors occurred at a higher prevalence among premenopausal African American patients compared with postmenopausal American and non-African American patients in this population-based study, and their associations with tumor size, axillary nodal status, mitotic index, nuclear pleomorphism, combined grade, p53 mutation status, and breast cancer-specific survival were examined.
Abstract: ContextGene expression analysis has identified several breast cancer subtypes, including basal-like, human epidermal growth factor receptor-2 positive/estrogen receptor negative (HER2+/ER–), luminal A, and luminal B.ObjectivesTo determine population-based distributions and clinical associations for breast cancer subtypes.Design, Setting, and ParticipantsImmunohistochemical surrogates for each subtype were applied to 496 incident cases of invasive breast cancer from the Carolina Breast Cancer Study (ascertained between May 1993 and December 1996), a population-based, case-control study that oversampled premenopausal and African American women. Subtype definitions were as follows: luminal A (ER+ and/or progesterone receptor positive [PR+], HER2−), luminal B (ER+ and/or PR+, HER2+), basal-like (ER−, PR−, HER2−, cytokeratin 5/6 positive, and/or HER1+), HER2+/ER− (ER−, PR−, and HER2+), and unclassified (negative for all 5 markers).Main Outcome MeasuresWe examined the prevalence of breast cancer subtypes within racial and menopausal subsets and determined their associations with tumor size, axillary nodal status, mitotic index, nuclear pleomorphism, combined grade, p53 mutation status, and breast cancer–specific survival.ResultsThe basal-like breast cancer subtype was more prevalent among premenopausal African American women (39%) compared with postmenopausal African American women (14%) and non–African American women (16%) of any age (P<.001), whereas the luminal A subtype was less prevalent (36% vs 59% and 54%, respectively). The HER2+/ER− subtype did not vary with race or menopausal status (6%-9%). Compared with luminal A, basal-like tumors had more TP53 mutations (44% vs 15%, P<.001), higher mitotic index (odds ratio [OR], 11.0; 95% confidence interval [CI], 5.6-21.7), more marked nuclear pleomorphism (OR, 9.7; 95% CI, 5.3-18.0), and higher combined grade (OR, 8.3; 95% CI, 4.4-15.6). Breast cancer–specific survival differed by subtype (P<.001), with shortest survival among HER2+/ER− and basal-like subtypes.ConclusionsBasal-like breast tumors occurred at a higher prevalence among premenopausal African American patients compared with postmenopausal African American and non–African American patients in this population-based study. A higher prevalence of basal-like breast tumors and a lower prevalence of luminal A tumors could contribute to the poor prognosis of young African American women with breast cancer.
3,634 citations
TL;DR: The role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.
Abstract: Short cationic amphiphilic peptides with antimicrobial and/or immunomodulatory activities are present in virtually every life form, as an important component of (innate) immune defenses. These host-defense peptides provide a template for two separate classes of antimicrobial drugs. Direct-acting antimicrobial host-defense peptides can be rapid-acting and potent, and possess an unusually broad spectrum of activity; consequently, they have prospects as new antibiotics, although clinical trials to date have shown efficacy only as topical agents. But for these compounds to fulfill their therapeutic promise and overcome clinical setbacks, further work is needed to understand their mechanisms of action and reduce the potential for unwanted toxicity, to make them more resistant to protease degradation and improve serum half-life, as well as to devise means of manufacturing them on a large scale in a consistent and cost-effective manner. In contrast, the role of cationic host-defense peptides in modulating the innate immune response and boosting infection-resolving immunity while dampening potentially harmful pro-inflammatory (septic) responses gives these peptides the potential to become an entirely new therapeutic approach against bacterial infections.
3,556 citations
Oregon Health & Science University1, Newcastle University2, Novartis3, University of Texas MD Anderson Cancer Center4, University of Düsseldorf5, Leipzig University6, Cornell University7, National Institutes of Health8, Harvard University9, University of Barcelona10, Heidelberg University11, Wake Forest University12, Icahn School of Medicine at Mount Sinai13, University of Paris14, University of Bordeaux15, Erasmus University Rotterdam16, Royal Adelaide Hospital17, Medical University of Vienna18, University of Mainz19, Katholieke Universiteit Leuven20, University of British Columbia21, University of Basel22, Aarhus University23, Fred Hutchinson Cancer Research Center24, Uppsala University25, Mater Health Services26, University of Bologna27, University of Chicago28
TL;DR: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients.
Abstract: BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa ...
3,351 citations
TL;DR: In conclusion, noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV‐coinfected patients.
3,183 citations
TL;DR: In the context of agricultural pest management, botanical insecticides are best suited for use in organic food production in industrialized countries but can play a much greater role in the production and postharvest protection of food in developing countries.
Abstract: Botanical insecticides have long been touted as attractive alternatives to synthetic chemical insecticides for pest management because botanicals reputedly pose little threat to the environment or to human health. The body of scientific literature documenting bioactivity of plant derivatives to arthropod pests continues to expand, yet only a handful of botanicals are currently used in agriculture in the industrialized world, and there are few prospects for commercial development of new botanical products. Pyrethrum and neem are well established commercially, pesticides based on plant essential oils have recently entered the marketplace, and the use of rotenone appears to be waning. A number of plant substances have been considered for use as insect antifeedants or repellents, but apart from some natural mosquito repellents, little commercial success has ensued for plant substances that modify arthropod behavior. Several factors appear to limit the success of botanicals, most notably regulatory barriers and the availability of competing products (newer synthetics, fermentation products, microbials) that are cost-effective and relatively safe compared with their predecessors. In the context of agricultural pest management, botanical insecticides are best suited for use in organic food production in industrialized countries but can play a much greater role in the production and postharvest protection of food in developing countries.
2,996 citations
TL;DR: The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides.
Abstract: Antimicrobial host defense peptides are produced by all complex organisms as well as some microbes and have diverse and complex antimicrobial activities. Collectively these peptides demonstrate a broad range of antiviral and antibacterial activities and modes of action, and it is important to distinguish between direct microbicidal and indirect activities against such pathogens. The structural requirements of peptides for antiviral and antibacterial activities are evaluated in light of the diverse set of primary and secondary structures described for host defense peptides. Peptides with antifungal and antiparasitic activities are discussed in less detail, although the broad-spectrum activities of such peptides indicate that they are important host defense molecules. Knowledge regarding the relationship between peptide structure and function as well as their mechanism of action is being applied in the design of antimicrobial peptide variants as potential novel therapeutic agents.
TL;DR: Tarin et al. as discussed by the authors described the process of epithelial-mesenchymal transition (EMT) as a defining structural feature of organ development and discussed its role in cancer and fibrosis, as well as identifying new markers to facilitate the observation of EMT in vivo.
Abstract: The conversion of an epithelial cell to a mesenchymal cell is critical to metazoan embryogenesis and a defining structural feature of organ development. Current interest in this process, which is described as an epithelial-mesenchymal transition (EMT), stems from its developmental importance and its involvement in several adult pathologies. Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada (October 1-3, 2005). The meeting, which was hosted by The EMT International Association, was the second international EMT meeting, the first being held in Port Douglas, Queensland, Australia in October 2003. The EMT International Association was formed in 2002 to provide an international body for those interested in EMT and the reverse process, mesenchymal-epithelial transition, and, most importantly, to bring together those working on EMT in development, cancer, fibrosis, and pathology. These themes continued during the recent meeting in Vancouver. Discussion at the Vancouver meeting spanned several areas of research, including signaling pathway activation of EMT and the transcription factors and gene targets involved. Also covered in detail was the basic cell biology of EMT and its role in cancer and fibrosis, as well as the identification of new markers to facilitate the observation of EMT in vivo. This is particularly important because the potential contribution of EMT during neoplasia is the subject of vigorous scientific debate (Tarin, D., E.W. Thompson, and D.F. Newgreen. 2005. Cancer Res. 65:5996-6000; Thompson, E.W., D.F. Newgreen, and D. Tarin. 2005. Cancer Res. 65:5991-5995).
TL;DR: It is demonstrated that in multiple FTD families with significant evidence for linkage to the same region on chromosome 17q21, FTD is caused by mutations in progranulin (PGRN) that are likely to create null alleles and identified mutations in PGRN as a cause of neurodegenerative disease.
Abstract: Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. A large proportion of FTD patients (35-50%) have a family history of dementia, consistent with a strong genetic component to the disease. In 1998, mutations in the gene encoding the microtubule-associated protein tau (MAPT) were shown to cause familial FTD with parkinsonism linked to chromosome 17q21 (FTDP-17). The neuropathology of patients with defined MAPT mutations is characterized by cytoplasmic neurofibrillary inclusions composed of hyperphosphorylated tau. However, in multiple FTD families with significant evidence for linkage to the same region on chromosome 17q21 (D17S1787-D17S806), mutations in MAPT have not been found and the patients consistently lack tau-immunoreactive inclusion pathology. In contrast, these patients have ubiquitin (ub)-immunoreactive neuronal cytoplasmic inclusions and characteristic lentiform ub-immunoreactive neuronal intranuclear inclusions. Here we demonstrate that in these families, FTD is caused by mutations in progranulin (PGRN) that are likely to create null alleles. PGRN is located 1.7 Mb centromeric of MAPT on chromosome 17q21.31 and encodes a 68.5-kDa secreted growth factor involved in the regulation of multiple processes including development, wound repair and inflammation. PGRN has also been strongly linked to tumorigenesis. Moreover, PGRN expression is increased in activated microglia in many neurodegenerative diseases including Creutzfeldt-Jakob disease, motor neuron disease and Alzheimer's disease. Our results identify mutations in PGRN as a cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival.
TL;DR: This is one of the first studies, in children or adults, to explore: (a) how memory requirements interact with spatial compatibility and (b) spatial incompatibility effects both with stimulus-specific rules (Simon task) and with higher-level, conceptual rules.
[...]
TL;DR: In this paper, the authors review the hypothesis that mind-wandering can be integrated into standard executive models of attention and show that it often occurs in the absence of explicit intention.
Abstract: This article reviews the hypothesis that mind wandering can be integrated into executive models of attention. Evidence suggests that mind wandering shares many similarities with traditional notions of executive control. When mind wandering occurs, the executive components of attention appear to shift away from the primary task, leading to failures in task performance and superficial representations of the external environment. One challenge for incorporating mind wandering into standard executive models is that it often occurs in the absence of explicit intention--a hallmark of controlled processing. However, mind wandering, like other goal-related processes, can be engaged without explicit awareness; thus, mind wandering can be seen as a goal-driven process, albeit one that is not directed toward the primary task.
TL;DR: A formal meta-analysis of studies that have experimentally manipulated species diversity to examine how it affects the functioning of numerous trophic groups in multiple types of ecosystem suggests that the average effect of decreasing species richness is to decrease the abundance or biomass of the focal Trophic group, leading to less complete depletion of resources used by that group.
Abstract: Over the past decade, accelerating rates of species extinction have prompted an increasing number of studies to reduce species diversityexperimentallyandexaminehowthisalterstheefficiency by which communities capture resources and convert those into biomass 1,2 . So far, the generality of patterns and processes observed in individual studies have been the subjects of considerable debate 3–7 .Here wepresent aformal meta-analysis of studies thathaveexperimentallymanipulatedspeciesdiversitytoexamine how it affects the functioning of numerous trophic groups in multiple types of ecosystem. We show that the average effect of decreasing species richness is to decrease the abundance or biomass of the focal trophic group, leading to less complete depletion of resources used by that group. At the same time, analyses reveal that the standing stock of, and resource depletion by, the most species-rich polyculture tends to be no different from that of the single most productive species used in an experiment. Of the known mechanisms that might explain these trends, results are most consistent with what is called the ‘sampling effect’, which occurs when diverse communities are more likely to contain and become dominated by the most productive species. Whether this mechanism is widespread in natural communities is currently controversial. Patterns we report are remarkably consistent for four different trophic groups (producers, herbivores, detritivores and predators) and two major ecosystem types (aquatic and terrestrial). Collectively, ouranalysessuggestthat theaverage species loss does indeed affect the functioning of a wide variety of organisms and ecosystems, but the magnitude of these effects is ultimatelydeterminedbytheidentityofspeciesthataregoingextinct.
TL;DR: In this paper, the authors propose a methodology to sample sequentially from a sequence of probability distributions that are defined on a common space, each distribution being known up to a normalizing constant.
Abstract: Summary. We propose a methodology to sample sequentially from a sequence of probability distributions that are defined on a common space, each distribution being known up to a normalizing constant. These probability distributions are approximated by a cloud of weighted random samples which are propagated over time by using sequential Monte Carlo methods. This methodology allows us to derive simple algorithms to make parallel Markov chain Monte Carlo algorithms interact to perform global optimization and sequential Bayesian estimation and to compute ratios of normalizing constants. We illustrate these algorithms for various integration tasks arising in the context of Bayesian inference.
TL;DR: More than 100 articles related to anode catalysts for the direct methanol fuel cell (DMFC) are reviewed, mainly focusing on the three most active areas: (1) progress in preparation methods of Pt-Ru catalysts with respect to activity improvement and utilization optimization; (2) preparation of novel carbon materials as catalyst supports to create a highly dispersed and stably supported catalysts; (3) exploration of new catalysts having a low noble metal content and non-noble metal elements through fast activity down-selection methods such as combinatorial methods.
TL;DR: The use of multi-parameter cell sorting and limiting dilution transplant analysis is reported to demonstrate the purification of a rare subset of adult mouse mammary cells that are able individually to regenerate an entire mammary gland within 6 weeks in vivo while simultaneously executing up to ten symmetrical self-renewal divisions.
Abstract: Elucidation of the cellular and molecular mechanisms that maintain mammary epithelial tissue integrity is of broad interest and paramount to the design of more effective treatments for breast cancer. Evidence from both in vitro and in vivo experiments suggests that mammary cell differentiation is a hierarchical process originating in an uncommitted stem cell with self-renewal potential. However, analysis of the properties and regulation of mammary stem cells has been limited by a lack of methods for their prospective isolation. Here we report the use of multi-parameter cell sorting and limiting dilution transplant analysis to demonstrate the purification of a rare subset of adult mouse mammary cells that are able individually to regenerate an entire mammary gland within 6 weeks in vivo while simultaneously executing up to ten symmetrical self-renewal divisions. These mammary stem cells are phenotypically distinct from and give rise to mammary epithelial progenitor cells that produce adherent colonies in vitro. The mammary stem cells are also a rapidly cycling population in the normal adult and have molecular features indicative of a basal position in the mammary epithelium.
TL;DR: A model of eHealth literacy is introduced, comprised of multiple literacy types, including an outline of a set of fundamental skills consumers require to derive direct benefits from eHealth.
Abstract: Electronic health tools provide little value if the intended users lack the skills to effectively engage them. With nearly half the adult population in the United States and Canada having literacy levels below what is needed to fully engage in an information-rich society, the implications for using information technology to promote health and aid in health care, or for eHealth, are considerable. Engaging with eHealth requires a skill set, or literacy, of its own. The concept of eHealth literacy is introduced and defined as the ability to seek, find, understand, and appraise health information from electronic sources and apply the knowledge gained to addressing or solving a health problem. In this paper, a model of eHealth literacy is introduced, comprised of multiple literacy types, including an outline of a set of fundamental skills consumers require to derive direct benefits from eHealth. A profile of each literacy type with examples of the problems patient-clients might present is provided along with a resource list to aid health practitioners in supporting literacy improvement with their patient-clients across each domain. Facets of the model are illustrated through a set of clinical cases to demonstrate how health practitioners can address eHealth literacy issues in clinical or public health practice. Potential future applications of the model are discussed.
[J Med Internet Res 2006;8(2):e9]
TL;DR: It is found that virulence factors that are required for the initiation of acute infections are often selected against during chronic infections, including cystic fibrosis patient's P. aeruginosa strains.
Abstract: In many human infections, hosts and pathogens coexist for years or decades. Important examples include HIV, herpes viruses, tuberculosis, leprosy, and malaria. With the exception of intensively studied viral infections such as HIV/AIDs, little is known about the extent to which the clonal expansion that occurs during long-term infection by pathogens involves important genetic adaptations. We report here a detailed, whole-genome analysis of one such infection, that of a cystic fibrosis (CF) patient by the opportunistic bacterial pathogen Pseudomonas aeruginosa. The bacteria underwent numerous genetic adaptations during 8 years of infection, as evidenced by a positive-selection signal across the genome and an overwhelming signal in specific genes, several of which are mutated during the course of most CF infections. Of particular interest is our finding that virulence factors that are required for the initiation of acute infections are often selected against during chronic infections. It is apparent that the genotypes of the P. aeruginosa strains present in advanced CF infections differ systematically from those of “wild-type” P. aeruginosa and that these differences may offer new opportunities for treatment of this chronic disease.
United States Department of Agriculture1, La Trobe University2, Grand Valley State University3, University of British Columbia4, Florida International University5, University of Gothenburg6, University of Alaska Fairbanks7, Abisko Scientific Research Station8, University of Virginia9, University Centre in Svalbard10, Colorado State University11, Michigan State University12, Marine Biological Laboratory13, University of California, Irvine14, United States Geological Survey15, Finnish Forest Research Institute16, Norwegian University of Life Sciences17, University of Colorado Boulder18, University of Stirling19
TL;DR: Warming increased height and cover of deciduous shrubs and graminoids, decreased cover of mosses and lichens, and decreased species diversity and evenness, which predict that warming will cause a decline in biodiversity across a wide variety of tundra, at least in the short term.
Abstract: Recent observations of changes in some tundra ecosystems appear to be responses to a warming climate. Several experimental studies have shown that tundra plants and ecosystems can respond strongly to environmental change, including warming; however, most studies were limited to a single location and were of short duration and based on a variety of experimental designs. In addition, comparisons among studies are difficult because a variety of techniques have been used to achieve experimental warming and different measurements have been used to assess responses. We used metaanalysis on plant community measurements from standardized warming experiments at 11 locations across the tundra biome involved in the International Tundra Experiment. The passive warming treatment increased plant-level air temperature by 1-3°C, which is in the range of predicted and observed warming for tundra regions. Responses were rapid and detected in whole plant communities after only two growing seasons. Overall, warming increased height and cover of deciduous shrubs and graminoids, decreased cover of mosses and lichens, and decreased species diversity and evenness. These results predict that warming will cause a decline in biodiversity across a wide variety of tundra, at least in the short term. They also provide rigorous experimental evidence that recently observed increases in shrub cover in many tundra regions are in response to climate warming. These changes have important implications for processes and interactions within tundra ecosystems and between tundra and the atmosphere.
TL;DR: In this paper, the authors evaluated the association between a single index of walkability that incorporated land use mix, street connectivity, net residential density, and retail floor area ratios, with health-related outcomes in King County, Washington.
Abstract: The literature shows single-use, low-density land development and disconnected street networks to be positively associated with auto dependence and negatively associated with walking and transit use. These factors in turn appear to affect health by influencing physical activity, obesity, and emissions of air pollutants. We evaluated the association between a single index of walkability that incorporated land use mix, street connectivity, net residential density, and retail floor area ratios, with health-related outcomes in King County, Washington. We found a 5% increase in walkability to be associated with a per capita 32.1% increase in time spent in physically active travel, a 0.23-point reduction in body mass index, 6.5% fewer vehicle miles traveled, 5.6% fewer grams of oxides of nitrogen (NOx) emitted, and 5.5% fewer grams of volatile organic compounds (VOC) emitted. These results connect development patterns with factors that affect several prevalent chronic diseases.
TL;DR: Results from clinical protocols using Tr1 cells to modulate immune responses in vivo in autoimmunity, transplantation, and chronic inflammatory diseases will undoubtedly prove the biological relevance of these cells in immunotolerance.
Abstract: Interleukin-10 (IL-10)-secreting T regulatory type 1 (Tr1) cells are defined by their specific cytokine production profile, which includes the secretion of high levels of IL-10 and transforming growth factor-beta(TGF-beta), and by their ability to suppress antigen-specific effector T-cell responses via a cytokine-dependent mechanism. In contrast to the naturally occurring CD4+ CD25+ T regulatory cells (Tregs) that emerge directly from the thymus, Tr1 cells are induced by antigen stimulation via an IL-10-dependent process in vitro and in vivo. Specialized IL-10-producing dendritic cells, such as those in an immature state or those modulated by tolerogenic stimuli, play a key role in this process. We propose to use the term Tr1 cells for all IL-10-producing T-cell populations that are induced by IL-10 and have regulatory activity. The full biological characterization of Tr1 cells has been hampered by the difficulty in generating these cells in vitro and by the lack of specific marker molecules. However, it is clear that Tr1 cells play a key role in regulating adaptive immune responses both in mice and in humans. Further work to delineate the specific molecular signature of Tr1 cells, to determine their relationship with CD4+ CD25+ Tregs, and to elucidate their respective role in maintaining peripheral tolerance is crucial to advance our knowledge on this Treg subset. Furthermore, results from clinical protocols using Tr1 cells to modulate immune responses in vivo in autoimmunity, transplantation, and chronic inflammatory diseases will undoubtedly prove the biological relevance of these cells in immunotolerance.
TL;DR: The authors proposed a conservative prior distribution for variance components, which deliberately gives more weight to smaller values and is appropriate for investigators who are skeptical about the presence of variability in the second-stage parameters (random effects).
Abstract: Bayesian hierarchical models typically involve specifying prior distributions for one or more variance components. This is rather removed from the observed data, so specification based on expert knowledge can be difficult. While there are suggestions for "default" priors in the literature, often a condi tionally conjugate inverse-gamma specification is used, despite documented drawbacks of this choice. The authors suggest "conservative" prior distributions for variance components, which deliberately give more weight to smaller values. These are appropriate for investigators who are skeptical about the presence of variability in the second-stage parameters (random effects) and want to particularly guard against inferring more structure than is really present. The suggested priors readily adapt to various hierarchical modelling settings, such as fitting smooth curves, modelling spatial variation and combining data from multiple sites. Lois a priori conservatrices pour les parametres de variance de modeles hierarchiques Rgsum6: Les modeles bay6siens hierarchiques comportent g6n6ralement une ou des composantes de va riance que l'on doit doter de lois a priori. Le choix de ces lois est delicat car la variation est un aspect des donn6es difficile a cemer. De toutes les lois a priori "par defaut," une loi conjuguee inverse-gamma con ditionnelle est la plus souvent employ6e, malgr6 ses inconvenients. Les auteurs proposent des lois a priori "conservatrices" pour les composantes de la variance qui privilegient les petites valeurs. Elles conviennent bien aux situations oiu le chercheur s'interroge sur la presence r6elle de variabilit6 dans les parametres de deuxieme degre (effets aleatoires) et qu'il veut eviter d'imposer une structure artificielle. Les lois a priori sugg6rdes s'adaptent A diverses situations propices a la mod6lisation hierarchique, notamment l'ajustement de courbes lisses et la modelisation de variation spatiale ou de donn6es issues de nombreux sites.
TL;DR: A trust-centered, cognitive and emotional balanced perspective to study RA adoption is taken, and the effects of perceived personalization and familiarity on cognitive trust and emotional trust in an RA are examined.
Abstract: In the context of personalization technologies, such as Web-based product-brokering recommendation agents (RAs) in electronic commerce, existing technology acceptance theories need to be expanded to take into account not only the cognitive beliefs leading to adoption behavior, but also the affect elicited by the personalized nature of the technology. This study takes a trust-centered, cognitive and emotional balanced perspective to study RA adoption. Grounded on the theory of reasoned action, the IT adoption literature, and the trust literature, this study theoretically articulates and empirically examines the effects of perceived personalization and familiarity on cognitive trust and emotional trust in an RA, and the impact of cognitive trust and emotional trust on the intention to adopt the RA either as a decision aid or as a delegated agent.
An experiment was conducted using two commercial RAs. PLS analysis results provide empirical support for the proposed theoretical perspective. Perceived personalization significantly increases customers' intention to adopt by increasing cognitive trust and emotional trust. Emotional trust plays an important role beyond cognitive trust in determining customers' intention to adopt. Emotional trust fully mediates the impact of cognitive trust on the intention to adopt the RA as a delegated agent, while it only partially mediates the impact of cognitive trust on the intention to adopt the RA as a decision aid. Familiarity increases the intention to adopt through cognitive trust and emotional trust.
TL;DR: The matrix metalloproteinases mediate homeostasis of the extracellular environment and have multiple signalling activities that are commonly altered during tumorigenesis and that might serve as intervention points for anticancer drugs.
Abstract: The matrix metalloproteinases (MMPs) mediate homeostasis of the extracellular environment. They have multiple signalling activities that are commonly altered during tumorigenesis and that might serve as intervention points for anticancer drugs. However, there are many criteria to consider in validating MMPs as drug targets and for the development of MMP inhibitors. The inhibition of some MMPs could have pro-tumorigenic effects (making them anti-targets), counterbalancing the benefits of target inhibition. These effects might partially account for the failure of MMP inhibitors in clinical trials. What are the major challenges in MMP target validation and MMP-inhibitor-drug development?
TL;DR: The results of nine experiments suggest that money brings about a self-sufficient orientation in which people prefer to be free of dependency and dependents.
Abstract: Money has been said to change people's motivation (mainly for the better) and their behavior toward others (mainly for the worse) The results of nine experiments suggest that money brings about a self-sufficient orientation in which people prefer to be free of dependency and dependents Reminders of money, relative to nonmoney reminders, led to reduced requests for help and reduced helpfulness toward others Relative to participants primed with neutral concepts, participants primed with money preferred to play alone, work alone, and put more physical distance between themselves and a new acquaintance
Max Planck Society1, University of Marburg2, Broad Institute3, Trent University4, University of Toronto5, California State University, Long Beach6, University of British Columbia7, University of Georgia8, University of Louisville9, Utrecht University10, Saint Joseph's University11, Spanish National Research Council12, Cornell University13, CINVESTAV14, University of Kentucky15, Duke University16, University of Valencia17, Saint Louis University18, Bayer19, Exelixis20, Technische Universität München21
TL;DR: The discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi.
Abstract: Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.
TL;DR: The meaning maintenance model proposes that people have a need to perceive events through a prism of mental representations of expected relations that organizes their perceptions of the world, and that when people's sense of meaning is threatened, they reaffirm alternative representations as a way to regain meaning-a process termed fluid compensation.
Abstract: The meaning maintenance model (MMM) proposes that people have a need for meaning; that is, a need to perceive events through a prism of mental representations of expected relations that organizes their perceptions of the world. When people's sense of meaning is threatened, they reaffirm alternative representations as a way to regain meaning-a process termed fluid compensation. According to the model, people can reaffirm meaning in domains that are different from the domain in which the threat occurred. Evidence for fluid compensation can be observed following a variety of psychological threats, including most especially threats to the self, such as self-esteem threats, feelings of uncertainty, interpersonal rejection, and mortality salience. People respond to these diverse threats in highly similar ways, which suggests that a range of psychological motivations are expressions of a singular impulse to generate and maintain a sense of meaning.